Incremental and decremental kinetics of gastric responses to infused gastrin in dogs

1982 ◽  
Vol 242 (6) ◽  
pp. G660-G667
Author(s):  
B. I. Hirschowitz
Keyword(s):  
Volume Of Distribution ◽  
Blood Levels ◽  
Published Data ◽  
Gastric Fistula ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Molar Basis ◽  
Human Gastrin ◽  
The Right ◽  
Kinetics Of

Acid and pepsin secretion was stimulated by graded doses of synthetic human gastrin I (G-17-I) and pentagastrin (G-5) in six conscious gastric fistula dogs, three with intact vagi and three with fundic vagotomy. Metabolic clearance rate of G-17 was 15.2 ml.kg-1.min-1 and volume of distribution was 15.8%. Gastrin levels decayed in two slopes: t1/2 of 6.8 min and 25-35 min, respectively. These were compared with other published data. Vmax was higher in intact stomachs and at doses or blood levels of gastrin about three to four times smaller. G-17 was almost four times more potent (molar basis) than G-5. Responses were log linearly related to G-17 dose and to serum G-17 during infusion (incremental) and after stopping infusion (decremental). Normalized decremental curves were congruent in all dogs but displaced fivefold (625 vs. 130 pmol/l) to the right at midpoint. Vagotomy changed only association (incremental) kinetics (Km = 352 pmol/l). The previously undescribed difference between blood concentration-effect relationship during drug administration and withdrawal may be important in situations in which blood levels are used as therapeutic guide.

Model of the distribution and metabolism of a GnRH superagonist in dogs

1990 ◽  
Vol 258 (3) ◽  
pp. E468-E475
Author(s):  
D. Lacoste ◽  
B. Candas ◽  
M. Normand ◽  
F. Labrie
Keyword(s):  
Apparent Volume ◽  
Volume Of Distribution ◽  
Gonadotropin Releasing Hormone ◽  
Metabolic Clearance ◽  
Sigmoid Function ◽  
Subcutaneous Route ◽  
Metabolic Clearance Rate ◽  
Fractional Rate ◽  
Kinetics Of ◽  
Apparent Volume Of Distribution

The plasma kinetics of [D-Trp6, des-Gly-NH2(10)]gonadotropin-releasing hormone (GnRH) ethylamide was assessed in eight dogs over a period of 8 h after rapid intravenous or subcutaneous injection. Each animal received doses of 0.2, 2, and 20 micrograms/kg body wt iv and 1 and 10 micrograms/kg body wt sc. A two-compartment structure, to which a source compartment was added to represent the subcutaneous route, adequately fits the five kinetics when the apparent volume of distribution follows a plasma concentration-dependent sigmoid function. Despite the nonlinearity, the apparent volume of distribution can be approximated by a constant value of 280 ml/kg body wt for the dynamics corresponding to the three lowest and more physiological doses. The metabolic clearance rate is 4.63 ml.min-1.kg body wt-1. The two exponential components that characterize the two-compartment structure are equal to 0.0348 +/- 0.0053 and 0.00470 +/- 0.00060 min-1, respectively. The agonist injected subcutaneously diffuses to plasma at a fractional rate of 0.0265 +/- 0.0029 min-1. Disposal occurs at a maximal rate of 0.017 and 0.0055 min-1 of the amount of agonist present in the central and peripheral compartments, respectively. The highest fractional exchange rate between compartments reaches 0.01 min-1. As simulated with the model, a continuous infusion of 4.63 ng.min-1.kg body wt-1 leads to a steady state of 1 ng/ml plasma; 90% of that level is reached 7 h after the onset of the subcutaneous input signal. The kinetics of plasma [D-Trp6, des-Gly-NH2(10)]GnRH ethylamide is many times slower than that of the native hormone and of the other GnRH agonists.

KINETICS OF 3H-TESTOSTERONE METABOLISM IN PATIENTS WITH CARCINOMA OF THE PROSTATE: EFFECTS OF OESTROGEN ADMINISTRATION

1971 ◽  
Vol 67 (4) ◽  
pp. 733-739 ◽  
Author(s):  
C. E. Bird ◽  
R. N. Green ◽  
R. S. Calandra ◽  
J. G. Connolly ◽  
A. F. Clark
Keyword(s):  
Beneficial Effect ◽  
Clearance Rate ◽  
Prostatic Carcinoma ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Oestrogen Therapy ◽  
Metabolic Clearance Rate ◽  
Testosterone Metabolism ◽  
Kinetics Of ◽  
Volumes Of Distribution

ABSTRACT We studied the effects of oestrogen administration on the kinetics of testosterone metabolism in patients with prostatic carcinoma. We investigated changes in the metabolic clearance rate, transport and metabolic rate constants and volumes of distribution. In all patients but one, the metabolic clearance rate and volumes of distribution were low during oestrogen administration. The beneficial effect of oestrogen therapy in patients with prostatic carcinoma may be related to the increase in the rate of testosterone metabolism (K2) within a smaller volume of distribution (V1).

Comparative metabolic clearance rate, volume of distribution and plasma half-life of human β-lipotropin and acth

Life Sciences ◽  
1978 ◽  
Vol 23 (23) ◽  
pp. 2323-2330 ◽  
Author(s):  
Anthony S. Liotta ◽  
Choh Hao Li ◽  
George C. Schussler ◽  
Dorothy T. Krieger
Keyword(s):  
Clearance Rate ◽  
Half Life ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Plasma Half Life

Pharmacokinetics and organ metabolism of carboxyamidated and glycine-extended gastrins in pigs

1996 ◽  
Vol 271 (1) ◽  
pp. G156-G163 ◽  
Author(s):  
C. P. Hansen ◽  
F. Stadil ◽  
L. Yucun ◽  
J. F. Rehfeld
Keyword(s):  
Clearance Rate ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Constant Rate Infusion ◽  
Constant Rate ◽  
Vascular Beds ◽  
Apparent Volume Of Distribution ◽  
Rate Infusion

The elimination of carboxyamidated gastrin-17 and its glycine-extended precursor was studied in anesthetized pigs during constant-rate infusion. Extraction of amidated gastrin-17 was recorded in the hindlimb (42%), kidney (40%), head (32%, P < 0.001), and the gut (13%, P < 0.01). Elimination was not recorded in the liver, lungs, or heart. Extraction of glycine-extended gastrin-17 was measured in the kidney (36%), hindlimb (31%, P < 0.001), head (26%), and the gut (16%, P < 0.01), but not in the liver or the lungs. Glycine-extended gastrin-17 was not processed to amidated gastrin during infusion. The half-life, metabolic clearance rate, and apparent volume of distribution for amidated gastrin-17 were 3.5 +/- 0.4 min, 15.5 +/- 1.1 ml.kg-1.min-1, and 76.5 +/- 9.9 ml/kg, respectively, and for glycine-extended gastrin-17 were 4.3 +/- 0.6 min, 17.4 +/- 0.9 ml.kg-1.min-1, and 104.7 +/- 11.9 ml/kg, respectively. We conclude that extraction of amidated and glycine-extended gastrin-17 varies in the vascular beds, with elimination mainly confined to nonorgan tissues and the kidneys.

Multiple cold air exposures change oral triiodothyronine kinetics in normal men

1992 ◽  
Vol 263 (1) ◽  
pp. E85-E93 ◽  
Author(s):  
H. L. Reed ◽  
M. M. D'Alesandro ◽  
K. R. Kowalski ◽  
L. D. Homer
Keyword(s):  
Cold Exposure ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Group Effect ◽  
Metabolic Clearance Rate ◽  
Free T4 ◽  
Cold Air ◽  
Normal Men ◽  
Serum Tsh

The influence of cold exposure on triiodothyronine (T3) kinetics was studied in 16 men before, during (biweekly), and after 80 (10/wk) cold (4 degrees C) air exposures. We used serum values before and up to 24 h after a pharmacological oral (o) dose of T3 [76.8 nmol (50 micrograms)] to calculate noncompartmental kinetic parameters. To assess the role of thyroxine (T4) and thyrotropin (TSH), we administered a replacement dose of T3 [46.0 nmol/day (30 micrograms)] to eight men (+T3 group) and placebo to eight others (-T3 group) for the 2-mo study. There was no group effect of T3 treatment (+T3) on oral total volume of distribution (TVdo), metabolic clearance rate (MCRo), or disposal rate (DRo). TVdo was not changed over the study. Cold increased MCRo by 5.4 +/- 2.0 l.day-1.m-2. DRo increased with cold by 10.2 +/- 4.4 nmol.day-1.m-2. Although serum TSH, total T4, and free T4 decreased by approximately 50% in the +T3 group, the changes in MCRo and DRo with cold were not different from those in -T3. We describe that human T3 kinetics are changed with brief repeated exposures to cold air and that these increases in MCRo and DRo do not appear to be dependent on TSH or T4.

Production rate, metabolic clearance rate and uterine extraction of corticosterone during rat pregnancy

1994 ◽  
Vol 143 (1) ◽  
pp. 183-190 ◽  
Author(s):  
B J Waddell ◽  
H C Atkinson
Keyword(s):  
Production Rate ◽  
Clearance Rate ◽  
Statistical Significance ◽  
Blood Levels ◽  
Additional Contribution ◽  
Metabolic Clearance ◽  
Maternal Weight ◽  
Metabolic Clearance Rate ◽  
Pregnant Rats ◽  
Conscious Rats

Abstract This study examined changes in the blood concentration of corticosterone with the onset and progression of pregnancy in the rat. To identify the source of variation in blood corticosterone, the metabolic clearance rate (MCR) and production rate of corticosterone were also determined. Measurements were made in conscious rats (n=4–7 per group) in the morning of dioestrus and days 5, 10, 16 and 22 of pregnancy (term=day 23). Corticosterone levels were 713 ±38 nmol/l (mean±s.e.m.) in non-pregnant rats, remained unchanged to day 10 of pregnancy, then increased to 1036 ± 52 nmol/l by day 16 and remained high at day 22. The production rate of corticosterone appeared to increase during pregnancy from 25·6±1·7 μmol/day on day 10 to reach 36·3±3·3 mol/day on day 22, but this did not reach statistical significance (one-way ANOVA). The MCR of corticosterone was similar among all groups (overall mean 34·6±2·5 1/day), although a slight but non-significant fall was apparent at day 16. When account was taken of changes in maternal weight, the MCR decreased progressively from 139± 10 1/day per kg before pregnancy to reach a minimum of 88 ±7 1/day per kg on day 16. Transuterine extraction of corticosterone on day 22 of pregnancy was 19·2±3·1% and so, based on this and estimates of uterine blood flow, the uterus must account for around 15% of corticosterone clearance at this time. Because this uterine contribution is effectively additional clearance, it is likely that without it the MCR of corticosterone would have fallen during pregnancy. Administration of ACTH (1–24) (3·5 nmol) increased the production rate of corticosterone at dioestrus and at day 16 of pregnancy, but this effect was less marked in the pregnant group (134% and 41% increase respectively). The MCR of corticosterone also rose (17%) following ACTH(1–24) administration in pregnant but not dioestrous rats. This difference in the MCR response is likely to reflect pregnancy-induced changes in the relative levels of corticosterone, progesterone and corticosteroid-binding globulin. In conclusion, this study shows that blood levels of corticosterone increase progressively during pregnancy in conscious rats. This increase apparently resulted from the net effects of increased production and decreased MCR, neither of which reached statistical significance. It would appear, however, that the trend toward increased production of corticosterone contributes more to the rise in blood corticosterone than does MCR, since the latter was more effectively maintained at pre-pregnancy levels. The demonstration of significant transuterine extraction of corticosterone at day 22 suggests that the maintenance of corticosterone clearance late in pregnancy is due, in part, to an additional contribution by the uterus and its contents. Journal of Endocrinology (1994) 143, 183–190

Effect of adrenal denervation on the glucose, insulin, and glucagon responses to exercise in sheep

1982 ◽  
Vol 60 (12) ◽  
pp. 1459-1463 ◽  
Author(s):  
Ronald P. Brockman
Keyword(s):  
Insulin Secretion ◽  
Adrenal Gland ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Hormonal Stimulation ◽  
Hormonal Responses ◽  
Exercise Induced ◽  
The Right ◽  
Induced Changes ◽  
Stimulation Of

Previous studies suggest that adrenal catecholamines mediate, in part, the glucose and pancreatic hormonal responses to exercise in sheep. This was examined in sheep whose adrenals were denervated to prevent stress-induced changes in catecholamine secretion. The innervation to the right adrenal gland was severed and the left adrenal was removed. Adrenal denervation was associated with a reduction in exercise-induced hyperglycemia and impairment, as measured by [2-3H]glucose, of the increase in glucose appearance during the first 10 min of exercise and increased metabolic clearance rate of glucose after 20 min of exercise. Insulin concentrations were significantly higher during exercise after adrenal denervation than in the controls. Adrenal denervation did not alter the rise in glucagon due to exercise. These effects are consistent with adrenomedullary hormonal stimulation of hepatic and muscular glycogenolysis, either directly or indirectly through the regulation of insulin secretion during exercise in sheep.

The Kinetics of Plasma Noradrenaline in Normal and Hypertensive Subjects

1978 ◽  
Vol 55 (s4) ◽  
pp. 89s-92s ◽  
Author(s):  
S. Ghione ◽  
C. Palombo ◽  
M. Pellegrini ◽  
E. Fommei ◽  
A. Pilo ◽  
...  
Keyword(s):  
Clearance Rate ◽  
Normal Subjects ◽  
Plasma Noradrenaline ◽  
Metabolic Clearance ◽  
Venous Sampling ◽  
Metabolic Clearance Rate ◽  
Hypertensive Patients ◽  
Arterial Blood ◽  
Endogenous Noradrenaline ◽  
Kinetics Of

1. The kinetics of plasma noradrenaline have been determined in normal and essential hypertensive patients by intravenous injection of tritiated noradrenaline and serial mixed venous sampling. 2. The metabolic clearance rate of plasma noradrenaline in normal subjects was approximately 1·1 min−1 m−2, whereas in essential hypertensive patients it was significantly reduced to approximately 0·61 min−1 m−2. 3. Metabolic clearance rate was negatively correlated to mean arterial blood pressure and total peripheral resistances. 4. Particularly low values of metabolic clearance rate were found in two patients with congestive heart failure and one with phaeochromocytoma. 5. We propose that the access of plasma noradrenaline to the main removal mechanisms takes place in competition with the flow of unlabelled endogenous noradrenaline directly released by nerve endings. The slower removal of plasma noradrenaline in essential hypertension could then express a larger release of endogenous noradrenaline in this condition.

Metabolic clearance rate in sheep of a met-enkephalin analogue estimated by radioimmunoassay

1982 ◽  
Vol 93 (3) ◽  
pp. 427-433 ◽  
Author(s):  
J. E. Bolton ◽  
J. H. Livesey ◽  
R. A. Donald
Keyword(s):  
Clearance Rate ◽  
Bolus Injection ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Time Intervals ◽  
Naturally Occurring ◽  
Specific Radioimmunoassay ◽  
The Mean

A sensitive and specific radioimmunoassay developed for measuring the met-enkephalin analogue d-ala2-met(0)5-ol-enkephalin (DAMME) was used to study the pharmacokinetics of DAMME in the circulation of sheep. Plasma concentrations of DAMME were measured at varying time-intervals after an intravenous bolus injection or following a constant intravenous infusion of the analogue. The mean metabolic clearance rate of DAMME was 2·8 ml/min per kg, the mean circulating half-life was 52 min and the mean volume of distribution was 190 ml/kg. The longer circulating time of the analogue when compared with that of naturally occurring met-enkephalin would appear to explain its prolonged analgesic effect.

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